crossing96/oncoscreening huggingface dataset:
Tumor microenvironment B cells increase bladder cancer metastasis via modulation of the IL-8/androgen receptor (AR)/MMPs signals.	While B cells in the tumor microenvironment may play important roles in cancer progression, their impacts on the bladder cancer (BCa) metastasis remain unclear. Here we found from human clinical BCa samples that BCa tissues could recruit more B cells than the surrounding normal bladder tissues and the in vitro co-culture assay also demonstrated that B cells could be recruited more easily towards BCa cells compared to normal bladder cells. Chamber invasion and 3D invasion assays showed the recruited B cells could then significantly increase the BCa cell invasion. Mechanism dissection found that recruited B cells could increase IL-8/androgen receptor (AR) signals in BCa cells that could then promote the expression of metastasis genes including MMP1 and MMP13. Blocking the IL-8/AR/MMPs signals either by anti-IL-8 neutralizing antibody, AR-siRNA, or MMPs inhibitors all partially reversed the infiltrating B cells capacity to increase the BCa cell invasion. The in vivo data from orthotopically xenografted BCa mouse model also confirmed that infiltrating B cells could increase BCa cell invasion via increasing AR signals. Together, these results demonstrate the key roles of B cells within the bladder tumor microenvironment that increase the BCa metastasis and may help us to develop the potential therapies via targeting these newly identified IL-8/AR/MMPs signals to better battle the BCa progression.	bladder
Meta-analysis of studies with bivariate binary outcomes: a marginal beta-binomial model approach.	When conducting a meta-analysis of studies with bivariate binary outcomes, challenges arise when the within-study correlation and between-study heterogeneity should be taken into account. In this paper, we propose a marginal beta-binomial model for the meta-analysis of studies with binary outcomes. This model is based on the composite likelihood approach and has several attractive features compared with the existing models such as bivariate generalized linear mixed model (Chu and Cole, 2006) and Sarmanov beta-binomial model (Chen et al., 2012). The advantages of the proposed marginal model include modeling the probabilities in the original scale, not requiring any transformation of probabilities or any link function, having closed-form expression of likelihood function, and no constraints on the correlation parameter. More importantly, because the marginal beta-binomial model is only based on the marginal distributions, it does not suffer from potential misspecification of the joint distribution of bivariate study-specific probabilities. Such misspecification is difficult to detect and can lead to biased inference using currents methods. We compare the performance of the marginal beta-binomial model with the bivariate generalized linear mixed model and the Sarmanov beta-binomial model by simulation studies. Interestingly, the results show that the marginal beta-binomial model performs better than the Sarmanov beta-binomial model, whether or not the true model is Sarmanov beta-binomial, and the marginal beta-binomial model is more robust than the bivariate generalized linear mixed model under model misspecifications. Two meta-analyses of diagnostic accuracy studies and a meta-analysis of case-control studies are conducted for illustration.	bladder
Improved 5-Factor Prognostic Classification of Patients Receiving Salvage Systemic Therapy for Advanced Urothelial Carcinoma.	PURPOSE: Prognostic factors in patients receiving salvage systemic therapy for advanced urothelial carcinoma include performance status, liver metastasis, hemoglobin and time since chemotherapy. We investigated the impact of albumin, and neutrophil, lymphocyte and platelet counts. MATERIALS AND METHODS: Patient level data from 10 phase II trials were used. Cox proportional hazards regression was applied to evaluate associations with overall survival. An optimal regression model was constructed using forward stepwise selection and risk groups were defined using the number of adverse factors. Trial was a stratification factor. External validation was done in a separate data set of 5 salvage phase II trials. RESULTS: Discovery data were obtained on 708 patients. After adjustment for the 4 known factors a platelet count of the upper limit of normal or greater and albumin less than the lower limit of normal were significant poor prognostic factors. Only the addition of albumin was externally validated. For 0 or 1, 2 and 3 or greater risk factors median overall survival was 8.9, 6.4 and 4.5 months in 207, 171 and 113 patients in the discovery data set of 491, and 10.6, 10.0 and 7.0 months in 73, 47 and 47 patients, respectively, in the validation data set of 167. By adding albumin the c-index improved from 0.610 to 0.639 in the discovery set and from 0.616 to 0.646 in the validation set. CONCLUSIONS: Albumin was externally validated as a prognostic factor for overall survival after accounting for time from prior chemotherapy, hemoglobin, performance status and liver metastasis status in patients receiving salvage systemic therapy for advanced urothelial carcinoma. The discovery of molecular prognostic factors is a priority to further enhance this new preferred 5-factor clinical prognostic model.	bladder
MiR-186 suppresses the growth and metastasis of bladder cancer by targeting NSBP1.	BACKGROUND: Increasing evidence has shown that microRNAs function as oncogenes or tumor suppressors in human malignancies, but the roles of miR-186 in human bladder cancer (BC) is still unclear. METHODS: First, quantitative real-time PCR (qRT-PCR) was performed to detect miR-186 expression in bladder cancer tissues and cell lines. Then, Bioinformatics analysis, combined with luciferase reporter assay demonstrated the target gene of miR-186. Finally, the roles of miR-186 in regulation of tumor proliferation and invasion were further investigated. RESULTS: Here, our study showed miR-186 was down-regulated in bladder cancer tissues and cell lines. Luciferase reporter assay showed that miR-186 targets NSBP1 3'-untranslated region (UTR) directly and suppresses NSBP1 (HMGN5) expression in human bladder cancer cells. NSBP1 siRNA- and miR-186-mediated NSBP1 knock-down experiments revealed that miR-186 suppresses cell proliferation and invasion through suppression of NSBP1 expression. Expression analysis of a set of epithelial-mesenchymal transition (EMT) markers showed that NSBP1 involves miR-186 suppressed EMT which reducing the expression of mesenchymal markers (vimentin and N-cadherin) and inducing the expression of epithelial marker (E-cadherin). CONCLUSIONS: Our data first time identified miR-186 as the upstream regulator of NSBP1 and also suggest miR-186-suppressed NSBP1 as a novel therapeutic approach for bladder cancer.	bladder
Clinical and therapeutic factors associated with adverse pathological outcomes in clinically node-negative patients treated with neoadjuvant cisplatin-based chemotherapy and radical cystectomy.	PURPOSE: Several disease characteristics have been identified as potential predictors for pathological node involvement (pN+) following radical cystectomy (RC). However, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). We endeavored to assess factors predicting adverse pathology in clinically node-negative patients treated with NAC and RC. METHODS: Patients from four North American institutions with cT2-4aN0M0 UC who received three or four cycles of NAC followed by RC were selected. Logistic regression was used to predict pN+, <pT2 and pT4 disease. RESULTS: One hundred and ninety-six patients were included. The clinical stage was cT2 in 115 (61 %), cT3 in 62 (33 %) and cT4 in 12 (6 %) cases. NAC regiments were gemcitabine-cisplatin (GC)-4 cycles 57 (29 %), GC-3 cycles 77 (39 %), methotrexate, vinblastine, adriamycin, cisplatin (MVAC)-3 cycle 22 (11 %) and MVAC-4 cycles 40 (21 %). pN+ was seen in 35 (18 %) patients. In the logistic regression analysis, cT4 stage (OR 7.50; 95 % CI 1.58-33.3) and three compared to four cycles of GC (OR 3.44; 95 % CI 1.09-10.9) were significant predictors of pN+ status. Additionally, when controlling for clinical stage, three cycles of GC, compared to four, were significantly associated with higher rates of pT4 disease and lower rates of downstaging to non-muscle-invasive disease. CONCLUSIONS: The results suggest that four cycles of neoadjuvant GC may be superior to three cycles, and the latter regimen may be associated with adverse pathological findings. Although this would require validation in a prospective trial, it does encourage the completion of the conventional four cycles GC whenever possible.	bladder
Role of Repeat Resection in Non-Muscle-Invasive Bladder Cancer.	Repeat transurethral resection (TUR) is indicated for high-grade non-muscle-invasive bladder tumors. Repeat TUR is a diagnostic, therapeutic, prognostic, and predictive procedure. Repeat TUR achieves optimal local control by removing residual tumors after initial TUR, improves staging accuracy, provides additional histologic material favoring accurate diagnosis, allocates appropriate therapy with improved outcomes, facilitates response to intravesical therapy, and provides important prognostic information.	bladder
[Prognostic factors for intravesical recurrence after surgery for upper tract urothelial carcinoma in renal transplant recipients].	OBJECTIVE: To elucidate clinicopathological independent prognostic factors for intravesical recurrence after nephroureterectomy for native upper tract urothelial carcinoma (UTUC) in renal transplant recipients. METHODS: In this study, 38 patients clinically diagnosed as localized UTUC after renal transplantation were included, and treated by retroperitoneal laparoscopic nephroureterectomy between April 2006 and March 2013, after exclusion of those with a previous and/or concurrent history of bladder cancer. The clinicopathologic features, risk factors, and intravesical recurrence free survival were analyzed using the Kaplan-Meier method. Univariate and multivariate analyses by Cox's proportional hazards regression model were used to identify independent risk factors for intravesical tumor recurrence. RESULTS: Of all the patients, 16/38 (42.1%) developed subsequent intravesical recurrence during a median follow-up period of 38 months (range 12 to 104 months), of whom, 12/16 (75.0%) developed recurrent bladder cancer within 2 years after nephroureterectomy, and the median interval between surgery and intravesical recurrence was 15.5 months (range 6 to 48 months). Multifocal tumors, native aristolochic acid nephropathy (AAN) and distal ureter involvement were determined as risk factors for intravesical recurrence by univariate analysis. The intravesical recurrence rate was 62.5% (5/8) in the group of native AAN, and 46.2% (12/26) in the group of multifocality. By multivariate analyses, multifocality (HR=2.603, 95% CI=1.529-8.906, P=0.019) and native AAN (HR=2.179, 95% CI=1.085-8.093, P=0.038) were identified as independent predictors for the development of recurrent bladder cancer after surgery for UTUC in renal transplant recipients. CONCLUSION: The incidence of intravesical recurrence after laparoscopic nephroureterectomy for UTUC in renal transplant recipients is high, and most subsequent bladder cancers recur within 2 years after surgery. Tumor multifocality and native AAN are significant independent risk factors in developing initial intravesical recurrence after laparoscopic surgery for primary UTUC after renal transplantation.	bladder
Genomic Characterization of Upper Tract Urothelial Carcinoma.	BACKGROUND: Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences. OBJECTIVE: To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity. DESIGN, SETTING, AND PARTICIPANTS: Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102). RESULTS AND LIMITATIONS: Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p<0.001), RB1 (0.0% vs 18.6%; p<0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed. CONCLUSIONS: High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma. PATIENT SUMMARY: Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies.	bladder
Bias-corrected estimates for logistic regression models for complex surveys with application to the United States' Nationwide Inpatient Sample.	For complex surveys with a binary outcome, logistic regression is widely used to model the outcome as a function of covariates. Complex survey sampling designs are typically stratified cluster samples, but consistent and asymptotically unbiased estimates of the logistic regression parameters can be obtained using weighted estimating equations (WEEs) under the naive assumption that subjects within a cluster are independent. Despite the relatively large samples typical of many complex surveys, with rare outcomes, many interaction terms, or analysis of subgroups, the logistic regression parameters estimates from WEE can be markedly biased, just as with independent samples. In this paper, we propose bias-corrected WEEs for complex survey data. The proposed method is motivated by a study of postoperative complications in laparoscopic cystectomy, using data from the 2009 United States' Nationwide Inpatient Sample complex survey of hospitals.	bladder
T-cell immunoglobulin mucin-3 expression in bladder urothelial carcinoma: Clinicopathologic correlations and association with survival.	BACKGROUND: T cell immunoglobulin mucin-3 (Tim-3) was initially recognized as a pivotal immune checkpoint inhibitor that maintains immune homeostasis and tolerance. Recently, Tim-3 has been demonstrated to play an important role in tumor-associated immune suppression and aberrant Tim-3 expression has been reported in several human malignancies. However, the role of Tim-3 in bladder urothelial carcinoma (BUC) remains largely unknown. The present study aims to investigate Tim-3 expression in BUC and analyze correlations with clinicopathologic outcomes and postoperative survival. METHODS: Tim-3 protein expressions were detected in paraffin embedded sections from 100 patients with BUC by immunohistochemistry. Expressions were correlated with clinicopathologic outcomes and postoperative survival. RESULTS: Tim-3 protein was over-expressed in bladder cancer cells, tumor infiltrating lymphocytes and endothelial cells from patients with BUC. The expression levels of Tim-3 were significantly correlated with advanced pathological grade and T stage. Moreover, another immune checkpoint molecule programmed death receptor-1(PD-1) was also over- expressed in BUC tissues and had a significant correlation with Tim-3. Multivariate analysis showed that Tim-3 expression, as well as PD-1 expression was both independent predictors of disease-free survival and overall survival in patients with BUC. CONCLUSION: Tim-3 over-expression implies adverse clinical outcomes for BUC, which suggests it is a potential prognostic biomarker and a novel therapeutic target in BUC.	bladder
Ossifying metaplasia of urothelial metastases: original case with review of the literature.	BACKGROUND: Ossifying metaplasia is an unusual feature of urothelial carcinoma, with only a few cases reported. The largest series included 17 cases and was published in 1991. The mechanism of ossification is unknown and hypotheses of osteogenic precursor cells, inducing bone formation, are proposed. CASE PRESENTATION: A 75 year-old patient was treated for a high grade transitional cell carcinoma of the bladder by surgery, chemotherapy and radiotherapy. Histology showed foci of bone metaplasia, both at the periphery of the tumor, and in a lymph node metastasis. 1 year later, a heterotopic bone formation was discovered in the right retroperitoneal space, near the lumbar spine, increasing rapidly in size during follow-up. Several imaging exams were performed (2 CT, 1 MRI, 1 Pet-CT), but in the absence of typical features of sarcoma, diagnosis remained unclear. Histology of a CT-guided percutaneous biopsy showed urothelial carcinoma and mature lamellar bone. Integration of these findings with the radiological description of extraosseous localization was consistent with a diagnosis of osseous metaplasia of an urothelial carcinoma metastasis. The absence of bone atypia in both the primary and metastases argues against sarcomatoid urothelial carcinoma with osteosarcomatous differentiation. CONCLUSION: Osseous metaplasia of an urothelial carcinoma metastasis is unusual, and difficult to distinguish from radiotherapy induced sarcoma, or from sarcomatoid carcinoma. Rapid progression, sheathing of adjacent structures such as vessels (like inferior vena cava in our case) and nerves and bony feature of lymph node metastases necessitate histological confirmation and rapid treatment. Our case illustrates this disease and evaluates the imaging features. In addition we discuss the differential diagnosis of osseous retroperitoneal masses.	bladder
Bilateral Iritis after Vaccine for Bladder Cancer.	PURPOSE: Bacille Calmette-Guérin (BCG) is a vaccine that can be instilled into the urinary bladder as immunotherapy against superficial bladder cancer. Several case reports have implicated intravesical BCG in the development of uveitis. Patients treated with BCG therapy may present with systemic symptoms resembling reactive arthritis and, less frequently, have ocular adverse effects including bilateral panuveitis or chorioretinitis. In all but three previously reported cases of uveitis associated with BCG treatment, HLA-B27 has been positive. No patients have been reported to be positive for rheumatoid factor or antinuclear antibody (ANA). CASE REPORT: An HLA-B27-negative and low-positive ANA patient presented with bilateral uveitis after treatment with BCG therapy for superficial bladder cancer. CONCLUSIONS: There is a need for greater awareness among urologists, primary care physicians, and optometrists of the potential for BCG to cause uveitis. These doctors should look for indicators of uveitis, such as circumlimbal conjunctival injection, photophobia, irregular pupils, and keratic precipitates. Together with appropriate treatment or prompt referral, this could prevent unnecessary morbidity. Future studies are needed to further elucidate the possible reasons for ANA positivity in these patients and the future role of the test in diagnosis and management.	bladder
TP53 and FGFR3 Gene Mutation Assessment in Urine: Pilot Study for Bladder Cancer Diagnosis.	AIM: To assess, in a prospective clinical research study, a new non-invasive and reliable test to accurately detect tumor protein 53 (TP53) and fibroblast growth factor receptor-3 (FGFR3) mutations in cells in urine. MATERIALS AND METHODS: TP53 mutations were analyzed using the functional analysis of separated allele in yeast (FASAY) method, which allows functional analysis of the P53 protein, and FGFR3 mutations were assessed with the SNaPshot system, detecting the eight most frequent point-mutations of this gene. Chi-square test or Fisher's exact test were used to compare TP53 and FGFR3 mutations in the tumors according to tumor stage and grade. RESULTS: TP53 and FGFR3 mutations in bladder tumors increased and decreased respectively with increasing tumor stage and cellular grade (p<0.05 and p<0.001, respectively). A total of 103 tumor/urinary sediment couples were analyzed. TP53 or FGFR3 mutations were observed in 76 tumors. The sensitivity for the detection of this type of mutation in urine was 46%, the specificity was 81%, the positive predictive value was 94% and the negative predictive value was 37%. CONCLUSION: Our original data confirmed the feasibility of TP53 and FGFR3 mutation detection in urine sediment. These measurements, together with urine cytology, may increase tumor detection. The sensitivity of the TP53/FGFR3 phenotype test in the urine was less than 50% and was not able to replace standard cystoscopy in the diagnosis of bladder tumors.	bladder
Serum miR-210 Contributes to Tumor Detection, Stage Prediction and Dynamic Surveillance in Patients with Bladder Cancer.	MiR-210 is the master hypoxamir that generally exhibits oncogenic properties in most human solid tumors including bladder cancer (BC). However, it remains unknown about the clinical significance of circulating miR-210 levels in BC. In this study, we found that serum miR-210 was up-regulated in patients with BC, and serum levels of miR-210 increased with advancing stage and grade. Moreover, serum miR-210 expression was found to be significantly reduced in paired post-operative samples and elevated in most patients with relapsed BC. Taken together, our data suggest that serum miR-210 could be a potential noninvasive biomarker for screening, predicting and monitoring BC.	bladder
Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion, and tumorigenesis in bladder carcinoma cells.	Growth differentiation factor-15 (GDF15), a member of the TGF-β superfamily, affects tumor biology of certain cancers, but remains poorly understood in bladder cancer cells. This study determined the expression, regulation, function, and potential downstream target genes of GDF15 in bladder carcinoma cells. The transitional papilloma carcionoma cells (RT4) expressed higher levels of GDF15 as compared with the bladder carcinoma cells (HT1376 and T24). Treatments of recombinant human GDF15 (rhGDF15) reduced the proliferations of HT1376 and T24 cells. Expression of GDF15 was upregulated via DNA demethylation and p53. The cell proliferation, invasion, and tumorigenesis were reduced in ectopic overexpression of GDF15, while enhanced in GDF15 knockdown. The expressions of mammary serine protease inhibitor (MASPIN) and N-myc downstream-regulated family genes (NDRG1, NDRG2, and NDRG3) were upregulated by GDF15 overexpressions and rhGDF15 treatments in bladder carcinoma cells. GDF15 knockdown induced epithelial-mesenchymal transition (EMT) and F-actin polarization in HT1376 cells. Our results suggest that enhanced expressions of MASPIN and N-myc downstream-regulated family genes and the modulation of EMT may account for the inhibitory functions of GDF15 in the cell proliferation, invasion, and tumorigenesis of bladder carcinoma cells. The GDF15 should be considered as a tumor suppressor in human bladder carcinoma cells.	bladder